Organic Molecular Cage Research Articles

A super large and robust free-standing organic cage membrane used for ultrasensitive solvent actuator

A robust free-standing organic cage membrane has been developed through a simple one-step solution-processing method of evaporation, which is fabricated by pure organic molecular cages and used without the addition of underlying support or polymer matrix. In addition, the organic cage membrane shows good mechanical stability, out-standing flexibility and self-healing performance. After 1,000,000 cycle bending tests, its mechanical properties are retentive, which provides the possibility of preparation of large dimension cage membranes (20 cm × 20 cm) and their derivatives in a simple way and hence shows promise in technical applications in separation, catalysis, and energy in the future. Then, a gradient structure is introduced into the membrane by quaternization reaction between the tertiary amine on the organic cages and methyl iodide. Thus, the membrane shows ultrasensitive gas and solvent stimuli responsive performance, which possesses the potential of monitoring the low portion of chloroform stimulus (0.61 mol%).

Single-Crystal Cage Framework with High Selectivity and Reversibility in Fullerene Binding.

Host-guest chemistry, a pivotal branch of supramolecular chemistry, plays an essential role in understanding and constructing complex structures through non-covalent interactions. Organic molecular cages, characterized by their intrinsic confined cavities, can selectively bind a variety of guest molecules. Their host-guest chemistry has been well studied in the solution phase, and several attempts have been made to encode well-defined molecular architectures into solid-state polymeric materials. However, only limited studies have explored their potential in the solid state, where their lack of robustness and less ordered networks significantly hinder practical applications. Herein, we report the synthesis of a single-crystal cage framework and a systematic study of its host-guest chemistry, spanning from the solution state to the solid state. Our studies reveal that the host-guest interactions inherent to the cage are successfully maintained in the solid-state polymeric material. Furthermore, the framework's robustness allows for the guest molecules (fullerene) to be released triggered by an organic acid (trifluoroacetic acid), with subsequent regeneration of the framework through an organic base (triethylamine) treatment. Our findings represent the first synthesis of a robust, single-crystal cage framework exhibiting highly selective and reversible host-guest chemistry, thus showing great potential towards molecular separation application.

Single‐Crystal Cage Framework with High Selectivity and Reversibility in Fullerene Binding

AbstractHost‐guest chemistry, a pivotal branch of supramolecular chemistry, plays an essential role in understanding and constructing complex structures through non‐covalent interactions. Organic molecular cages, characterized by their intrinsic confined cavities, can selectively bind a variety of guest molecules. Their host–guest chemistry has been well studied in the solution phase, and several attempts have been made to encode well‐defined molecular architectures into solid‐state polymeric materials. However, only limited studies have explored their potential in the solid state, where their lack of robustness and less ordered networks significantly hinder practical applications. Herein, we report the synthesis of a single‐crystal cage framework and a systematic study of its host–guest chemistry, spanning from the solution state to the solid state. Our studies reveal that the host–guest interactions inherent to the cage are successfully maintained in the solid‐state polymeric material. Furthermore, the framework's robustness allows for the guest molecules (fullerene) to be released triggered by an organic acid (trifluoroacetic acid), with subsequent regeneration of the framework through an organic base (triethylamine) treatment. Our findings represent the first synthesis of a robust, single‐crystal cage framework exhibiting highly selective and reversible host–guest chemistry, thus showing great potential towards molecular separation application.

Penetrative Ionic Organic Molecular Cage Nanozyme for the Targeted Treatment of Keratomycosis.

Keratomycosis, caused by pathogenic fungi, is an intractable blinding eye disease. Corneal penetration is an essential requirement for conventional antifungal medications to address keratomycosis. Due to the distinctive anatomical and physiological structure of the cornea, the therapeutic efficacy is hampered by the inadequate penetration capacity. Despite the emergence of diverse antifungal drug delivery systems and advanced antifungal nanomaterials, it has remained challenging to achieve corneal penetration over the past decade. This study fabricates a penetrative ionic organic molecular cage-based nanozyme (OMCzyme) for treating keratomycosis. The synthesis of OMCzyme involved two steps. Initially, the ionic OMC is synthesized by a [2+3] cycloimination reaction of triformylphloroglucinol and 2,3-diaminopropionic acid. Subsequently, OMCzyme is fabricated by coordination of Fe2⁺ with carboxyl anions and phenolic hydroxyls in the organic cage, and further deposition of silver nanoparticles on the surface of OMC-Fe complex. The as-prepared OMCzyme demonstrates excellent water dispersion, peroxidase-like activity, in vitro and in vivo biocompatibility, and corneal penetration. Notably, the nanozyme displays targeted antifungal activity, effectively combating Fusarium solani with negligible cytotoxicity toward human corneal epithelial cells. The hybrid mimic is further demonstrated to be effective in treating keratomycosis in mice, indicating the potential of OMCzyme for curing fungal infectious diseases.

Artificial transmembrane channel constructed from shape-persistent covalent organic molecular cages capable of ion and small molecule transport

Shape-persistent arylene ethynylene molecular cages have been investigated as transmembrane channels for ions and small molecules. The molecular cages were obtained starting from tetrayne monomers through alkyne metathesis cyclooligomerization. We found these porphyrin-based rigid molecular cages can insert into the lipid bilayer and efficiently transport ions and small molecules (e.g., calcein). Our study reveals longer hydrophobic alkyl chains on the cage molecule promote the channeling efficiency, while shorter and/or more polar side chains impair such activity. Kinetic analysis shows linear correlation between the rate of proton transport and the concentration of the cage, suggesting the active species is likely a monomeric cage. We found that C70-encapsulated cages are nearly inactive for transmembrane ion transportation, indicating that ions are likely transported through the internal cavity of the cage. Discrete shape-persistent organic cages represent highly stable synthetic ion channels or pores, which could have interesting applications in biomimetic signaling and drug delivery.

Reticular Modulation of Piezofluorochromic Behaviors in Organic Molecular Cages by Replacing Non‐Luminous Components

AbstractOrganic piezochromic materials that manifest pressure‐stimuli‐responses are important in various fields such as data storage and anticounterfeiting. The manipulation of piezofluorochromic behaviors for these materials is promising but remains a great challenge. Herein, a non‐luminous components regulated strategy is developed and organic molecular cages (OMCs), a burgeoning class of crystalline organic materials with structural dynamics, are first explored for the design of piezofluorochromic materials with tunable luminescence. A series of OMCs based on aggregation‐induced emission (AIE) chromophores, termed Cage 1–3, are synthesized and their piezofluorochromic behaviors are investigated by diamond anvil cell technique. Due to the sufficient voids between its flexible chromophores offered by the OMC structure, Cage 1 exhibits thermofluorochromic and piezofluorochromic properties. Moreover, the piezofluorochromic performance of this OMC could be further promoted by replacing its non‐luminous components with improved flexibilities, and a remarkable luminescence peak shift by 150 nm together with a response sensitivity of 13.8 nm GPa−1 was achieved upon hydrostatic compression. The cage structure plays a vital role in facilitating efficient and reversible piezofluorochromic behaviors. This study has shed light on the rational design and exploitation of OMCs as an exceptional platform to accomplish customizable piezofluorochromic behaviors and enlarge their potential applications in pressure‐based luminescence.

Reticular Modulation of Piezofluorochromic Behaviors in Organic Molecular Cages by Replacing Non-Luminous Components.

Organic piezochromic materials that manifest pressure-stimuli-responses are important in various fields such as data storage and anticounterfeiting. The manipulation of piezofluorochromic behaviors for these materials is promising but remains a great challenge. Herein, a non-luminous components regulated strategy is developed and organic molecular cages (OMCs), a burgeoning class of crystalline organic materials with structural dynamics, are first explored for the design of piezofluorochromic materials with tunable luminescence. A series of OMCs based on aggregation-induced emission (AIE) chromophores, termed Cage 1-3, are synthesized and their piezofluorochromic behaviors are investigated by diamond anvil cell technique. Due to the sufficient voids between its flexible chromophores offered by the OMC structure, Cage 1 exhibits thermofluorochromic and piezofluorochromic properties. Moreover, the piezofluorochromic performance of this OMC could be further promoted by replacing its non-luminous components with improved flexibilities, and a remarkable luminescence peak shift by 150 nm together with a response sensitivity of 13.8 nm GPa-1 was achieved upon hydrostatic compression. The cage structure plays a vital role in facilitating efficient and reversible piezofluorochromic behaviors. This study has shed light on the rational design and exploitation of OMCs as an exceptional platform to accomplish customizable piezofluorochromic behaviors and enlarge their potential applications in pressure-based luminescence.

Self-similar chiral organic molecular cages

The endeavor to enhance utility of organic molecular cages involves the evolution of them into higher-level chiral superstructures with self-similar, presenting a meaningful yet challenging. In this work, 2D tri-bladed propeller-shaped triphenylbenzene serves as building blocks to synthesize a racemic 3D tri-bladed propeller-shaped helical molecular cage. This cage, in turn, acts as a building block for a pair of higher-level 3D tri-bladed chiral helical molecular cages, featuring multilayer sandwich structures and displaying elegant characteristics with self-similarity in discrete superstructures at different levels. The evolutionary procession of higher-level cages reveals intramolecular self-shielding effects and exclusive chiral narcissistic self-sorting behaviors. Enantiomers higher-level cages can be interconverted by introducing an excess of corresponding chiral cyclohexanediamine. In the solid state, higher-level cages self-assemble into supramolecular architectures of L-helical or D-helical nanofibers, achieving the scale transformation of chiral characteristics from chiral atoms to microscopic and then to mesoscopic levels.

Comparing organic and metallo-organic hydrazone molecular cages as potential carriers for doxorubicin delivery.

Molecular cages are three-dimensional supramolecular structures that completely wrap guest molecules by encapsulation. We describe a rare comparative study between a metallo-organic cage and a fully organic analogous system, obtained by hydrazone bond formation self-assembly. Both cages are able to encapsulate the anticancer drug doxorubicin, with the organic cage forming a 1 : 1 inclusion complex with μM affinity, whereas the metallo-organic host experiences disassembly by interaction with the drug. Stability experiments reveal that the ligands of the metallo-organic cage are displaced in buffer at neutral, acidic, and basic pH, while the organic cage only disassembles under acidic conditions. Notably, the organic cage also shows minimal cell toxicity, even at high doses, whilst the doxorubicin-cage complex shows in vitro anti-cancer activity. Collectively, these results show that the attributes of the pure organic molecular cage are suitable for the future challenges of in vivo drug delivery using molecular cages.

A chiral emissive porous organic cage used for high-resolution gas chromatography separations

The illustration of a chiral and porous tubular organic molecular cage (3P-1) was obtained through a [3+6] imine condensation reaction that used as the chiral stationary phase for preparing a 3P-1-coated capillary column by the static coating method.

Pushing the Boundaries of Covalent Organic Frameworks through Postsynthetic Linker Exchange

AbstractCovalent organic frameworks (COFs) are a fast‐developing family of porous organic materials that have received substantial research interest during the last two decades. Dynamic covalent chemistry (DCC) is the cornerstone of COF fabrication. DCC is a process that entails reversible bond breaking‐reforming under equilibrium to attain the thermodynamically most stable structure. Due to the reversible nature of the covalent linkages, the building blocks of pre‐synthesized COF or pre‐assembled chemical entities, like network polymers and supramolecular hosts, can be replaced postsynthetically under appropriate reaction conditions. The technique is known as postsynthetic linker exchange (PLE). PLE provides an easy way to introduce functional building blocks into the COF backbone and control its chemical and physical properties. In this article, we have highlighted the recent advancements (from 2017 to 2023) in the postsynthetic linker exchange strategy for constructing highly crystalline and porous COFs that are often unattainable via de novo fabrication. The mechanistic insights of the linker exchange process for transforming various parent entities, such as COFs, amorphous covalent organic networks, linear polymers, and molecular cages to daughter COFs, have been deliberated with fascinating examples. We have also outlined some future avenues for applying the PLE process for the large‐scale fabrication of highly crystalline COFs for real‐time applications.

Mixed-matrix membranes comprising porous organic molecular cage for efficient CO2 capture

Membrane-based separation technology exhibits significant potential in the fields of CO2 capture and gas purification. Mixed-matrix membranes (MMMs) integrate the easy processing of polymeric materials with excellent transport properties of fillers, and thereby have become a focus for the next-generation gas separation membranes. Herein, we demonstrated a novel mixed-matrix membrane comprising porous organic molecular cages (POCs) and amine-rich polyvinylamine (PVAm) polymer matrix for efficient CO2 separation. Micro-sized CC3 crystals featuring a pore size of ∼4.9 Å, a high micropore volume of 0.16 cm3 g−1 and specific surface area of 326 m2 g−1 were synthesized and immobilized onto the surface of the PVAm thin selective layer to generate rapid CO2-transport channels. The resulting CC3/PVAm/mPSf MMM displayed excellent binary gas mixture (CO2/N2 15/85 vol %) separation performance, with a high CO2 permeance of 1546 GPU, and appreciable CO2/N2 selectivity of 33 at 1.5 bar, which was superior to most reported POCs-based membranes and thin film composite membranes, accompanied with excellent long-term operational stability. The CO2-selective separation facilitated by the incorporation of POCs provided a new inspiration for the development of novel MMMs for efficient CO2 capture.

SbPh3-based organic molecular cage for size-controlled preparation and stabilization of palladium nanoparticles

Group 15 triphenyl compounds with coordination ability such as triphenylamine (NPh3) and triphenylphosphine (PPh3) have been widely investigated for the construction of functional porous organic materials. In this work, a SbPh3-based organic molecular cage (Sb-cage) was unprecedently synthesized. The spatial configuration of Sb-cage was precisely analyzed by single crystal X-ray diffraction, showing a trigonal–bipyramidal [2 + 3] assembly. Sb-cage was employed to the mediated growth of palladium nanoparticles (PdNPs) with an average diameter of 0.70 nm. As-synthesized utrafine PdNPs exhibits good catalytic activity in Suzuki-Miyaura coupling reaction between aryl halides and phenylboronic acid, where the PdNPs could grow up in situ to a stable size distribution of 1.71 ± 0.30 nm. Furthermore, the advantages of the trigonal bipyramidal configuration in the stabilization of metal nanoparticles during the catalytic reaction cycles were demonstrated via the control experiments on SbPh3-based unclosed semicage.

Chiral Molecular Cage with Tunable Stereoinversion Barriers.

The manipulation of chirality in molecular entities that rapidly interconvert between enantiomeric forms is challenging, particularly at the supramolecular level. Advances in controlling such dynamic stereochemical systems offer opportunities to understand chiral symmetry breaking and homochirality. Herein, we report the synthesis of a face-rotating tetrahedron (FRT), an organic molecular cage composed of tridurylborane facial units that undergo stereomutations between enantiomeric trefoil propeller-like conformations. After resolution, we show that the racemization barrier of the enantiopure FRT can be regulated in situ through the reversible binding of fluoride anions onto the tridurylborane moieties. Furthermore, the addition of an enantiopure phenylethanol to the FRT can effectively induce chirality of the molecular cage by preferentially binding to one of its enantiomeric conformers. This study presents a new paradigm for controlling dynamic chirality in supramolecular systems, which may have implications for asymmetric synthesis and dynamic stereochemistry.

Homochiral organic molecular cage RCC3-R-modified silica as a new multimodal and multifunctional stationary phase for high-performance liquid chromatography.

In this work, homochiral reduced imine cage was covalently bonded to the surface of the silica to prepare a novel high-performance liquid chromatography stationary phase, which was applied for the multiple separation modes such as normal phase, reversed-phase, ion exchange, and hydrophilic interaction chromatography. The successful preparation of the homochiral reduced imine cage bonded silica stationary phase was confirmed by performing a series of methods including X-ray photoelectron spectroscopy, thermogravimetric analysis, and infrared spectroscopy. From the extracted results of the chiral resolution in normal phase and reversed-phase modes, it was demonstrated that seven chiral compounds were successfully separated, among which the resolution of 1-phenylethanol reached the value of 3.97. Moreover, the multifunctional chromatographic performance of the new molecular cage stationary phase was systematically investigated in the modes of reversed-phase, ion exchange, and hydrophilic interaction chromatography for the separation and analysis of a total of 59 compounds in eight classes. This work demonstrated that the homochiral reduced imine cage not only achieved multiseparation modes and multiseparation functions performance with high stability, but also expanded the application of the organic molecular cage in the field of liquid chromatography.

Transformation of an Imine Cage to a Covalent Organic Framework Film at the Liquid-Liquid Interface.

Dynamic covalent chemistry (DCC) opens up a fascinating route for the construction of well-organized supramolecular architectures, starting from organic molecular cages to crystalline macromolecular covalent organic frameworks (COFs). Herein, for the first time, we have manifested a facile room-temperature DCC-directed transformation of discrete organic imine cage-to-COF film at the liquid-liquid interface. The unfolding of the cage leading to the generation of imine intermediates, followed by their interface-assisted preorganization and subsequent growth of the COF film, are elucidated through detailed spectroscopic and microscopic investigations. The interfacial cage-to-COF transformation provides a facile route for the faster fabrication of free-standing COF films with high porosity and crystallinity, demonstrating excellent performance towards molecular sieving and high solvent permeance. Thus, the current study opens up a new route for structural interconversion between two crystalline entities with diverse dimensionality employing DCC at the confined interface.

Transformation of an Imine Cage to a Covalent Organic Framework Film at the Liquid–Liquid Interface

AbstractDynamic covalent chemistry (DCC) opens up a fascinating route for the construction of well‐organized supramolecular architectures, starting from organic molecular cages to crystalline macromolecular covalent organic frameworks (COFs). Herein, for the first time, we have manifested a facile room‐temperature DCC‐directed transformation of discrete organic imine cage‐to‐COF film at the liquid–liquid interface. The unfolding of the cage leading to the generation of imine intermediates, followed by their interface‐assisted preorganization and subsequent growth of the COF film, are elucidated through detailed spectroscopic and microscopic investigations. The interfacial cage‐to‐COF transformation provides a facile route for the faster fabrication of free‐standing COF films with high porosity and crystallinity, demonstrating excellent performance towards molecular sieving and high solvent permeance. Thus, the current study opens up a new route for structural interconversion between two crystalline entities with diverse dimensionality employing DCC at the confined interface.

Chiral emissive porous organic cages.

A pair of chiral, emissive and porous tubular multi-functional organic molecular cages were synthesized easily by imine chemistry of 4,4',4'',4'''-(ethene-1,1,2,2-tetrayl)-tetrabenzaldehyde (ETTBA) with (R,R)- or (S,S)-diaminocyclohexane (CHDA). It was found that the chirality of CHDA was transferred and amplified to tetraphenylethylene (TPE) in the process of formation of cages, which further endowed the cages with circularly polarized luminescence (CPL) characteristics. As a result of the synergy of the chirality and porous structure in the solid state, both cages exhibited a good chiral adsorption enantioselectivity to a series of aromatic racemates.

Efficient Multigram Procedure for the Synthesis of Large Hydrazone-linked Molecular Cages.

Covalently linked molecular cages can provide significant advantages (including, but not limited to enhanced thermal and chemical stability) over metal-linked coordination cages. Yet, while large coordination cages can now be created routinely, it is still challenging to create chemically robust, covalently linked molecular cages with large internal cavities. This fundamental challenge has made it difficult, for example, to introduce endohedral functional groups into covalent cages to enhance their practical utility (e.g., for selective guest recognition or catalysis), since the cavities would have simply been filled up with such endohedral functional groups in most cases. Here we now report the synthesis of some of the largest known covalently linked molecular tetrahedra. Our new covalent cages all contain 12 peripheral functional groups, which keep them soluble. They are formed from a common vertex, which aligns the hydrazide functions required for the hydrazone linkages with atropisomerism. While we previously reported this vertex as a building block for the smallest member of our hydrazone-linked tetrahedra, our original synthesis was not feasible to be carried out on the larger scales required to successfully access the larger tetrahedra. To overcome this synthetic challenge, we now present a greatly improved synthesis of our vertex, which only requires a single chromatographic step (compared to 3 chromatographic purification steps, which were needed for the initial synthesis). Our new synthetic route enabled us to create a whole family of molecular cages with increasing size (all linked with hydrolytically stable hydrazone bonds), with our largest covalent cage featuring p-quarterphenyl linkers and the ability to encapsulate a hypothetical sphere of approximately 3 nm in diameter. These results now open up the possibility to introduce functional groups required for selective recognition and catalysis into chemically robust covalent cages (without blocking the cavities of the covalent cages).

Soluble porous organic cages as homogenizers and electron-acceptors for homogenization of heterogeneous alloy nanoparticle catalysts with enhanced catalytic activity

The creation of ultrafine alloy nanoparticles (<5 nm) that can maintain surface activity and avoid aggregation for heterogeneous catalysis has received much attention and is extremely challenging. Here, ultrafine PtRh alloy nanoparticles imprisoned by the cavities of reduced chiral covalent imine cage (PtRh@RCC3) are prepared successfully by an organic molecular cage (OMC) confinement strategy, while the soluble RCC3 can act as a homogenizer to homogenize the heterogeneous PtRh alloy in solution. Moreover, the X-ray absorption near-edge structure (XANES) results show that the RCC3 can act as an electron-acceptor to withdraw electrons from Pt, leading to the formation of higher valence Pt atoms, which is beneficial to improving the catalytic activity for the reduction of 4-nitrophenol. Attributed to the synergistic effect of Pt/Rh atoms and the unique function of the RCC3, the reaction rate constants of Pt1Rh16@RCC3 are 49.6, 8.2, and 5.5 times than those of the Pt1Rh16 bulk, Pt@RCC3 and Rh@RCC3, respectively. This work provides a feasible strategy to homogenize heterogeneous alloy nanoparticle catalysts in solution, showing huge potential for advanced catalytic application.